FIGURE 3.

Schematic representation of the possible effects of intermittent fasting (IF) as an adjuvant treatment to partially rescue hypothalamic responses in obesity. Once IF prevents the pro-inflammatory effects in the hippocampus caused by LPS (29), and it is also able to increase the production of β-Hydroxybutyrate (βHB) (136), correlated to inflammatory control (134) and insulin sensitivity, it is possible to hypothesize that modulations in the microbiota may be helpful to reduce hypothalamic inflammation and increase hormonal sensitivity. Low serum leptin and insulin values during fasting contribute to an increase in the expression of AgRP and NPY. However, interestingly, the NPY mRNA expression returned to baseline values as a chronic response to IF, which may be is an adaptation to hunger. Furthermore, some studies found an increase in the expression of POMC neuropeptide, which is controversial. Such neuronal sensitivity to the IF protocol is perhaps also associated with better regulation of hypothalamic autophagic response since IF can activate the autophagic pathway in other tissues (146), and autophagic flux is an essential mediator of neuropeptide responses.